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Humanization of a mouse monoclonal antibody neutralizing TNF-alpha by guided selection
Wang, ZZ1; Wang, Y1; Li, ZF1; Li, J1; Dong, ZW1
关键词Tumor Necrosis Factor Alpha Phage Display Recombinant Antibody Libraries Human Antibody
刊名JOURNAL OF IMMUNOLOGICAL METHODS
2000-07-31
241期:1-2页:171-184
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemical Research Methods ; Immunology
研究领域[WOS]Biochemistry & Molecular Biology ; Immunology
关键词[WOS]TUMOR-NECROSIS-FACTOR ; HYPERVARIABLE REGIONS ; RHEUMATOID-ARTHRITIS ; FAB FRAGMENTS ; V(H) SEGMENTS ; SEPTIC SHOCK ; REPERTOIRE ; LIBRARIES ; AFFINITY ; REVEALS
英文摘要

With the advent of phage display antibody libraries, humanization of murine antibodies can be achieved by epitope guided selection. In present study, guided selection was applied to the humanization of the mouse mAb Z8 that is directed to human TNF-alpha and can neutralize the cytotoxicity of TNF-alpha. First, the Z8 Fd gene was paired as a template with a repertoire of human kappa chains, and displayed on the filamentous phage, forming a hybrid phage antibody library. Selected by four rounds of panning against TNF-alpha, hybrid antibody fragments that bound to TNF-alpha and contained human kappa chains were obtained. Meanwhile human Fd genes were selected by pairing the human Fd repertoire with the Z8 kappa chain and performing the same procedure of panning. One of the isolated human Fd genes (huFd2), which showed the strongest reactivity, was chosen to pair with 12 of selected human kappa chains. Two of the resulting human Fabs (huFd2-hu kappa 1 and huFd2-hu kappa 2), with same Fd and different kappa chains, bound to TNF-alpha specifically. Their human origin was proved by ELISA and sequencing analysis. The human Fabs competitive ELISA and in vitro TNF-alpha neutralization assay demonstrated that the human Fabs resembled its parental mouse mAb Z8 in that they both recognized the same epitope and neutralized the cytotoxicity of TNF-alpha. These results suggest that guided selection is a promising strategy in murine mAb humanization. (C) 2000 Elsevier Science BN. All rights reserved.

语种英语
WOS记录号WOS:000088641200016
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被引频次:15[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/51520
专题北京大学临床肿瘤学院
作者单位1.Navy Gen Hosp, Cent Lab, Beijing 100037, Peoples R China
2.Beijing Med Univ, Beijing Inst Canc Res, Beijing 100034, Peoples R China
3.Canc Hosp, Chinese Acad Med Sci, Beijing 100020, Peoples R China
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GB/T 7714
Wang, ZZ,Wang, Y,Li, ZF,et al. Humanization of a mouse monoclonal antibody neutralizing TNF-alpha by guided selection[J]. JOURNAL OF IMMUNOLOGICAL METHODS,2000,241(1-2):171-184.
APA Wang, ZZ,Wang, Y,Li, ZF,Li, J,&Dong, ZW.(2000).Humanization of a mouse monoclonal antibody neutralizing TNF-alpha by guided selection.JOURNAL OF IMMUNOLOGICAL METHODS,241(1-2),171-184.
MLA Wang, ZZ,et al."Humanization of a mouse monoclonal antibody neutralizing TNF-alpha by guided selection".JOURNAL OF IMMUNOLOGICAL METHODS 241.1-2(2000):171-184.
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